The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats.
The nitroxyl donor, Angeli's salt, inhibits inflammatory hyperalgesia in rats.
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DOI：
10.1016/j.neuropharm.2013.03.009
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发表时间：
2013-08
影响因子：
4.7
通讯作者：
Verri WA Jr
中科院分区：
文献类型：
--
作者：
Zarpelon AC;Souza GR;Cunha TM;Schivo IR;Marchesi M;Casagrande R;Pinge-Filho P;Cunha FQ;Ferreira SH;Miranda KM;Verri WA Jr
一氧化氮调节疼痛的发展。然而，没有证据表明硝酰基（HNO/NO−）在伤害感受中的作用。因此，我们解决了是否硝酰基抑制炎性痛觉过敏及其机制，使用硝酰基供体Angeli的盐（AS; Na 2N 2 O3）。机械性痛觉过敏进行了评估，使用改良的Randall和Selitto方法在大鼠中，细胞因子的ELISA和硝酰基的产生，通过共聚焦显微镜在NH 4Cl（一种细胞渗透性试剂，转化为一种荧光分子的氮氧化物）处理的培养的背根神经节神经元中测定。AS局部预处理（17- 450 µg/爪，30 min）以剂量和时间依赖性方式抑制角叉菜胶诱导的机械性痛觉过敏，最大抑制率为97%。AS还抑制角叉菜胶诱导的细胞因子产生。AS可抑制脂多糖、肿瘤坏死因子-α、白细胞介素-1 β和前列腺素E2等炎症刺激引起的痛敏。此外，用ODQ（一种可溶性鸟苷酸环化酶抑制剂）、KT 5823（一种蛋白激酶G [PKG]抑制剂）或格列本脲（一种ATP敏感性K+通道阻滞剂）治疗可阻止AS的镇痛作用，但用纳洛酮（一种阿片受体拮抗剂）治疗无效。AS以L-半胱氨酸（硝酰基清除剂）敏感的方式诱导DAF处理的神经元荧光强度的浓度依赖性增加。L-半胱氨酸不影响NO+供体S-亚硝基-N-乙酰-DL-青霉胺（SNAP）诱导的DAF处理的神经元的抗痛觉过敏或荧光。这是第一个研究表明，硝酰基抑制炎性痛觉过敏，通过减少细胞因子的产生和激活cGMP/PKG/ATP敏感的K+通道信号通路在体内。
Nitric oxide modulates pain development. However, there is no evidence on the effect of nitroxyl (HNO/NO−) in nociception. Therefore, we addressed whether nitroxyl inhibits inflammatory hyperalgesia and its mechanism using the nitroxyl donor Angeli’s salt (AS; Na2N2O3). Mechanical hyperalgesia was evaluated using a modified Randall and Selitto method in rats, cytokine production by ELISA and nitroxyl was determined by confocal microscopy in DAF (a cell permeable reagent that is converted into a fluorescent molecule by nitrogen oxides)-treated dorsal root ganglia neurons in culture. Local pre-treatment with AS (17– 450 µg/paw, 30 min) inhibited the carrageenin-induced mechanical hyperalgesia in a dose- and time-dependent manner with maximum inhibition of 97%. AS also inhibited carrageenin-induced cytokine production. AS inhibited the hyperalgesia induced by other inflammatory stimuli including lipopolysaccharide, tumor necrosis factor-α, interleukin-1β and prostaglandin E2. Furthermore, the analgesic effect of AS was prevented by treatment with ODQ (a soluble guanylate cyclase inhibitor), KT5823 (a protein kinase G [PKG] inhibitor) or glybenclamide (an ATP-sensitive K+ channel blocker), but not with naloxone (an opioid receptor antagonist). AS induced concentration-dependent increase in fluorescence intensity of DAF-treated neurons in a L-cysteine (nitroxyl scavenger) sensitive manner. L-cysteine did not affect the NO+ donor S-Nitroso-N-acetyl-DL- penicillamine (SNAP)-induced anti-hyperalgesia or fluorescence of DAF-treated neurons. This is the first study to demonstrate that nitroxyl inhibits inflammatory hyperalgesia by reducing cytokine production and activating the cGMP/PKG/ATP-sensitive K+ channel signaling pathway in vivo.
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影响因子：
3.9
作者：
ARNELLE, DR;STAMLER, JS
通讯作者：
STAMLER, JS
DOI：
10.1073/pnas.91.23.10992
发表时间：
1994-11-08
影响因子：
11.1
作者：
HOBBS, AJ;FUKUTO, JM;IGNARRO, LJ
通讯作者：
IGNARRO, LJ
影响因子：
8.3
作者：
Irvine, JC;Favaloro, JL;Kemp-Harper, BK
通讯作者：
Kemp-Harper, BK
影响因子：
5
作者：
FERREIRA, SH;LORENZETTI, BB;CORREA, FMA
通讯作者：
CORREA, FMA
DOI：
10.1038/newbio240200a0
发表时间：
1972-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
FERREIRA, SH
通讯作者：
FERREIRA, SH